Ionic Liquid Aided [¹¹C]CO Fixation for Synthesis of ¹¹C-carbonyls

Tributyl(ethyl)phosphonium oxopentenolate ([P₄₄₄₂][Pen]) is an ionic liquid developed to capture CO and has shown ability to catalyze carbonylation reactions in organic chemistry. Carbon-11 (¹¹C, t_1/2=20.4 min) labeled CO is a highly versatile building block for the synthesis of positron emission tomography (PET) radiotracers that are applied for medical imaging. The use of [¹¹C]CO is limited by its low solubility in organic solvents. Herein, we report a proof-of-concept study evaluating a new method to prepare ¹¹C-labeled amides, ureas and carbamates via reaction of [¹¹C]CO in [P₄₄₄₂][Pen] and applied for fully automated radiosyntheses of Bruton's tyrosine kinase inhibitors, [¹¹C]evobrutinib and [¹¹C]ibrutinib.